1. Field of the Invention
The present invention relates to novel hIL-4 mutant proteins, to processes for preparing them, and to their use as medicaments, in particular in association with overshooting, falsely regulated immune reactions and autoimmune diseases.
2. Description of Related Art
PCT WO 93/10235 already discloses therapeutic agents which are or which contain antagonists or partial agonists of hIL-4, with the antagonists or partial agonists being hIL-4 mutant proteins.
Human interleukin 4 hIL-4) is one of the many cytokines which induce and coordinate the proliferation, maturation, survival and differentiation of lymphoid and myeloid cells. In particular, hIL-4 is involved in the IgE-mediated immune reaction and directly accelerates the proliferation of thymocytes and activated T cells. A high-affinity IL-4 receptor protein of Mr 140,000 has been identified which, according to its cDNA sequence, consists of 800 amino acid residues. This protein belongs to a recently described group of receptors which are designated the haematopoietin receptor superfamily.
Based on the cloned cDNA, the amino acid sequence of the mature IL-4 consists of 129 residues. The cDNA has been expressed in E. coli and yeast. Recombinant IL-4 having high biological activity can be isolated from these sources.
Very recently, a monoclonal antibody has been disclosed which exhibits antagonistic properties towards human interleukin 4. This antibody contains a Fab fragment and is produced by a human/human hybridoma cell line. A hybridoma cell line from the spleen cells of a rat which was immunized against (non-)glycosylated human IL-4 also produces monoclonal antibodies against hIL-4.
The role of interleukin 4 in allergic processes provides grounds for hoping that substances which inhibit interleukin 4-mediated processes, or compete with hIL4, might interrupt the disease-triggering reaction chain.
DE 41 37 333 A1 describes hIL-4 mutant proteins in which the amino acid(s) occurring naturally in the wild type at one or more of positions 120, 121, 122, 123, 124, 125, 126, 127 or 128 has/have been replaced with one or more, respectively, of the other possible natural amino acids. These hIL-4 mutant proteins are antagonists or partial agonists of human IL-4.